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Evidence for sympathetic neurotransmission through presynaptic N‐type calcium channels in human saphenous vein
Author(s) -
Fabi Fulvia,
Chiavarelli Mario,
Argiolas Livio,
Chiavarelli Roberto,
Basso Paola
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13814.x
Subject(s) - neurotransmission , guanethidine , voltage dependent calcium channel , verapamil , tetrodotoxin , calcium , medicine , endocrinology , phentolamine , chemistry , neuromuscular transmission , neurotoxin , muscle contraction , biology , stimulation , receptor
1 The specific type(s) of voltage‐sensitive calcium channels (VSCCs) involved in sympathetic neurotransmission have not yet been characterized in human vascular tissues. We therefore examined the functional role of the N‐ and L‐type VSCCs in human saphenous veins. 2 Contractile response curves for transmural nerve stimulation (TNS) and for exogenously administered noradrenaline (NA) were obtained in superfused saphenous vein rings. The contractions induced by TNS, but not by NA, were inhibited by 1 μ m tetrodotoxin and by 10 μ m guanethidine. Both responses were substantially reduced by 1 μ m phentolamine, indicating that the contractions evoked by TNS were mediated by endogenous NA released from noradrenergic nerves. 3 In the presence of 2 μ m ω‐conotoxin GVIA (omega Conus Geographus toxin, fraction VI A; ω‐CgTx), a polypeptide with specific inhibitory activity on N‐ and L‐type calcium channels, the neurally evoked contractions were almost completely abolished. In contrast, the responses induced by exogenous NA were not affected by the neurotoxin, thus providing evidence of the exclusive presynaptic action of ω‐CgTx. 4 In the presence of the calcium antagonist verapamil (10 μ m ), which selectively blocks L‐type VSCCs, the contractions induced by both TNS and NA were diminished to the same extent, suggesting that the organic calcium blocker is active only at the postjunctional level. 5 It is concluded that N‐type calcium channels are the main pathway of calcium entry controlling the functional responses induced by activating sympathetic nerves; the role of L‐type channels appears to be limited to the postjunctional level, modulating smooth muscle contractions.